Sherbrooke Molecular Imaging Center, Research Center of the Sherbrooke University Hospital (CRCHUS), and Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Sherbrooke Molecular Imaging Center, Research Center of the Sherbrooke University Hospital (CRCHUS), and Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada
J Nucl Med. 2018 Feb;59(2):197-203. doi: 10.2967/jnumed.117.194654. Epub 2017 Aug 10.
After encouraging preclinical and human dosimetry results for the novel estrogen receptor (ER) PET radiotracer 4-fluoro-11β-methoxy-16α-F-fluoroestradiol (F-4FMFES), a phase II clinical trial was initiated to compare the PET imaging diagnostic potential of F-4FMFES with that of 16α-F-fluoroestradiol (F-FES) in ER-positive (ER+) breast cancer patients. Patients diagnosed with ER+ breast cancer ( = 31) were recruited for this study, including 6 who underwent mastectomy or axillary node dissection. For each patient, F-FES and F-4FMFES PET/CT scans were done sequentially (within a week) and in random order. One hour after injection of either radiotracer, a head-to-thigh static scan with a 2-min acquisition per bed position was obtained. Blood samples were taken at different times after injection to assess each tracer metabolism by reverse-phase thin-layer chromatography. The SUV of nonspecific tissues and the SUV of the tumor were evaluated for each detected lesion, and tumor-to-nonspecific organ ratios were calculated. Blood metabolite analysis 60 min after injection of the tracer showed a 2.5-fold increase in metabolic stability of F-4FMFES over F-FES. Although for most foci F-4FMFES PET had an SUV similar to that of F-FES PET, tumor contrast improved substantially in all cases. Lower uptake was consistently observed in nonspecific tissues for F-4FMFES, notably a 4-fold decrease in blood-pool activity as compared with F-FES. Consequently, image quality was considerably improved using F-4FMFES, with lower overall background activity. As a result, F-4FMFES successfully identified 9 more lesions than F-FES. This phase II study with ER+ breast cancer patients showed that F-4FMFES PET achieves a lower nonspecific signal and better tumor contrast than F-FES PET, resulting in improved diagnostic confidence and lower false-negative diagnoses.
在新型雌激素受体 (ER) PET 放射性示踪剂 4-氟-11β-甲氧基-16α-F-氟雌二醇 (F-4FMFES) 的临床前和人体剂量测定结果令人鼓舞后，启动了一项 II 期临床试验，以比较 F-4FMFES 与 16α-F-氟雌二醇 (F-FES) 在 ER 阳性 (ER+) 乳腺癌患者中的 PET 成像诊断潜力。 本研究招募了 31 名诊断为 ER+乳腺癌的患者，其中 6 名患者接受了乳房切除术或腋窝淋巴结清扫术。每位患者均先后（一周内）以随机顺序进行 F-FES 和 F-4FMFES PET/CT 扫描。在注射示踪剂后 1 小时，进行从头至大腿的静态扫描，每个床位位置采集 2 分钟。在注射后不同时间采集血样，通过反相薄层层析法评估每种示踪剂的代谢情况。评估每个检测到的病变的非特异性组织 SUV 和肿瘤 SUV，并计算肿瘤与非特异性器官的比值。 注射示踪剂后 60 分钟的血液代谢物分析显示，F-4FMFES 的代谢稳定性比 F-FES 高 2.5 倍。尽管对于大多数病灶，F-4FMFES PET 的 SUV 与 F-FES PET 相似，但所有病例的肿瘤对比度均显著提高。F-4FMFES 在非特异性组织中的摄取始终较低，与 F-FES 相比，血池活性降低了 4 倍。因此，使用 F-4FMFES 可显著提高图像质量，总体背景活动较低。结果，F-4FMFES 比 F-FES 成功识别出 9 个以上的病变。 这项针对 ER+乳腺癌患者的 II 期研究表明，F-4FMFES PET 比 F-FES PET 获得的非特异性信号更低，肿瘤对比度更好，从而提高了诊断信心，降低了假阴性诊断的风险。
